结直肠癌组织中MMR蛋白表达、MSI、RAS和BRAF基因突变与临床病理特征的关系OACSTPCD
Relationship between mismatch repair protein expression,MSI,RAS and BRAF gene mutation in colorectal cancer tissues with clinicopathological characteristics
目的 探讨结直肠癌患者癌组织中错配修复(MMR)蛋白表达、微卫星不稳定性(MSI)、大鼠肉瘤(RAS)基因和致癌同源体B1(BRAF)基因突变与临床病理特征的关系.方法 选取该院2022年1-12月接受根治手术治疗的352例结直肠癌患者的肿瘤组织和血液标本、42例非肠癌患者的实体瘤组织和血液标本,采用免疫组化法检测MMR蛋白表达,一代测序片段分析法检测MSI,实时荧光定量聚合酶链反应检测KRAS、NRAS和BRAF基因突变状态,分析MMR蛋白表达、MSI和3种基因突变状态与结直肠癌临床病理特征的关系.结果 352例CRC患者肿瘤组织中检出MMR缺陷(dMMR)29例(8.2%),高度微卫星不稳定(MSI-H)26例(7.4%),KRAS基因突变161例(45.7%),NRAS基因突变13例(3.7%),BRAF基因突变11例(3.1%).与dMMR有关因素为低龄、黏液腺癌、原发于右半结肠癌(P<0.05);与MSI-H相关因素包括低龄、肿瘤家族史、原发于右半结肠癌(P<0.05);KRAS和NRAS基因高突变率分别与黏液腺癌和淋巴结转移有关(P<0.05);BRAF基因高突变率与低分化和原发于右半结肠癌有关(P<0.05).BRAF基因突变与dMMR和MSI-H有关(P<0.05).结论 MMR蛋白表达,MSI,以及KRAS、NRAS和BRAF基因突变与不同的临床病理特征有关.通过这5种分子标志物的联合检测可以对肿瘤进行分子分型,进一步为结直肠癌患者的个体化精准诊疗提供理论依据.
Objective To investigate the relationship between the mismatch repair protein(MMR protein)expression,microsatellite instability(MSI),rat sarcoma gene(RAS)and carcinogenic homolog B1 gene(BRAF)gene mutation in colorectal cancer(CRC)tissues with the clinicopathologic features.Methods The tumor tissue and blood samples in 352 patients with colorectal cancer receiving the radical operation treatment and the mass tumor tissue and blood samples in 42 patients with non-intestinal cancer in this hospital from January to December 2022 were collected.The immunohistochemistry was used to detect the MMR protein,the first generation sequencing fragment analysis was performed to detect MSI,and the real-time quantitative PCR was used to detect the gene mutation status of KRAS,NRAS and BRAF.The relationship between MMR protein expression,MSI and three gene mutation states with the clinicopathologic features of CRC was ana-lyzed.Results In the tumor tissues of 352 patients with CRC,the 29 cases(8.2%)of MMR(dMMR)and 26 cases(7.4%)of MSI-H were detected respectively.The mutation rates of KRAS,NRAS,BRAF genes were 45.7%(161 cases),3.7%(13 cases)and 3.1%(11 cases),respectively.The factors associated with dMMR were the age,mucinous carcinoma and originated from right-sided colon cancer.The factors associated with MSI-H included the low age,family tumor history and originated from right-sided colon cancer(P<0.05).High mutation rates of KRAS and NRAS genes were related with mucinous adenocarcinoma and lymph node metastasis,respectively.High BRAF mutation rate was associated with poor differentiation and originated from fright-sided colon cancer(P<0.05).The BRAF gene mutation was related with dMMR and MSI-H.Conclusion The MMR protein expression,MSI status,and the gene mutations of KRAS,NRAS and BRAF are correlated with different clinicopathologic features.The combined detection of these five molecular mark-ers could be used to classify the tumor molecules,which further provides the theoretical basis for the individu-alized precision diagnosis and treatment of the patients with CRC.
向林果;谭憬一;姚远;孙雪琴;张阳丽
重庆医科大学附属第一医院临床分子医学检测中心,重庆 400016
临床医学
结直肠癌大鼠肉瘤基因致癌同源体B1基因错配修复蛋白微卫星不稳定性基因突变
colorectal cancerrat sarcoma genecarcinogenic homolog B1 genemismatch repair proteinmicrosatellite instabilitygene mutation
《检验医学与临床》 2024 (001)
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重庆市科卫联合医学科研项目(2020FYYX145).
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